DESCRIPTION: (Adapted from the application) The goal of this application for a Mid-career Award for Patient-Oriented Research is to support a substantial redirection of the investigators professional academic career development to focus on hypothesis-driven investigator-initiated clinical pharmacology research in conjunction with a substantive increase in mentoring of fellows and junior faculty engaged in patient-oriented research. Specifically, this award has the following aims: 1. Establish a more focused line of pharmacologic research which, building upon the candidate s existing pharmacologic research efforts, will begin with a new long-term project to define the pharmacokinetics of antiretroviral drugs in relation to the pharmacodynamic effects of these drugs on HIV burden in each of several compartments of the genital tract with the purpose of optimizing antiretroviral regimens for both the prevention of transmission and eradication of HIV from pharmacologic sanctuaries; 2. Provide a broader number of clinical researchers with the educational and logistical support of the Clinical Pharmacology Research Unit which has been organized to facilitate the efficient design, execution, analysis, and reporting of hypothesis-driven pharmacokinetic and pharmacodynamic research studies across numerous therapeutic disciplines; and 3. Provide enhanced one-on-one mentorship to junior faculty and post-doctoral fellows to establish the foundations of productive academic research careers in patient-oriented research.This award will allow the candidate to relinquish substantial current administrative and contract-research duties that have taken time away from his research goals and from mentoring junior physician-scientists interested in clinical investigation. The protected time that the award provides will allow him to expand his current research efforts with a more consolidated focus on the novel use of HIV-related drugs and on new clinical research projects with potential for substantial impact on the HIV epidemic. Simultaneously, the award will allow the candidate to increase the time can spend fostering the development of junior investigators through more intensive mentorship activities in the context of this research.